Urinary Cotinine Measurements Research Articles

Environmental Tobacco Smoke May Induce Early Lung Damage in Healthy Male Adolescents

Childhood exposure to environmental tobacco smoke (ETS) adversely affects dynamic spirometric indexes as a result of combined early life (including in utero) and current exposure to parental smoking. The aim of our study was to investigate the effect of ETS on lung function and to identify the most sensitive functional parameter for evaluating lung damage. Cross-sectional survey. Health survey on secondary school children. Eighty adolescents boys (mean age +/- SD, 16 +/- 1 years) classified in three groups: 21 smokers, 30 nonsmokers, and 29 passive smokers. Standardized questionnaire on the smoking habits of the subjects and their parents; assay of urinary cotinine level and measurement of the cotinine/creatine ratio (CCR); and lung function tests, including measurements of lung volumes, spirometric dynamic parameters, and the single-breath diffusing capacity of the lung for carbon monoxide (DLCO). Passive smokers presented a higher residual volume than nonsmokers, and a lower maximal expiratory flow at 25% of FVC (MEF(25)) and DLCO. Passive smokers whose mothers had smoked during pregnancy had significantly lower MEF(25) percentage, DLCO, carbon monoxide transfer coefficient, and diffusion capacity of the alveolar-capillary membrane (DM) values than did passive smokers whose mothers had given up smoking during pregnancy. Nevertheless, the MEF(25) and DM values of subjects with mothers who had given up smoking during pregnancy were lower than those observed in nonsmokers (p < 0.05), suggesting a negative effect of passive smoking independent of the mother's smoking habit during pregnancy. A statistically significant, negative correlation was found between CCR and DLCO in smokers (r = - 0.63, p < 0.01) and in passive smokers (r = - 0.91, p < 0.001), but not in nonsmokers (r = 0.26, p = not significant), suggesting a dose-effect relationship. Current exposure to ETS in healthy male adolescents is associated with lung function impairment independently of the effects of maternal smoking during pregnancy. More information may be obtained from determining static lung volumes and DLCO.

Environmental tobacco smoke exposure in low-income 6-year-olds: parent report and urine cotinine measures.

We examined the prevalence and level of environmental tobacco smoke (ETS) exposure using urine cotinine levels in children and three types of maternal self-reports in a sample of 196 low socioeconomic status (SES) mothers and their children. The self-reports were report of the mother's own smoking, report of the number of household smokers, and report of the usual number of daily hours that the child was exposed to ETS. According to the reports, 59% of the children's mothers were current smokers, 71% of the children came from households with smokers, and 85% had daily exposure to ETS. Based on urine cotinine measures adjusted for creatinine, 79% of the children were identified as ETS exposed. The average urine cotinine level was 19.6 ng/mg, and the median cotinine level was 13.1 ng/mg (range: 0-120 ng/mg). Correlations between urine cotinine levels and the three maternal reports were 0.48, 0.43, and 0.36, respectively. The most sensitive maternal report measure was number of hours of exposure per day when using adjusted urine cotinine levels of >/=5 ng/mg were used as the yardstick of exposure. Of the 154 children screened at the level of >/=5 ng/mg, 89.5% were also identified by maternal report as ETS exposed. However, 30 children whose mothers reported ETS exposure had urine cotinine levels of <5 ng/mg. These data showed that ETS exposure was prevalent in low-SES children and that the maternal reports identified a higher number of children as ETS exposed. The biological measures provided data on levels of recent exposure; however, level of exposure from biological measures correlated only moderately with the maternal report. A combination of a maternal report and a biological measure is suggested as the most informative estimate of ETS exposure in young children.

Environmental tobacco smoke exposure in low-income 6-year-olds: Parent report and urine cotinine measures

Environmental tobacco smoke exposure in low-income 6-year-olds: Parent report and urine cotinine measures

Tobacco smoke and formation of N-(2-hydroxyethyl)valine in human hemoglobin.

Human exposure to ethylene oxide (EtO) occurs mainly through inhalation of polluted air in occupational workplaces and/or via tobacco smoke. A significant biochemical reaction of EtO converts the terminal valine of hemoglobin into N-(2-hydroxyethyl)valine (HOEtVal). In the present study, the extent of HOEtVal formation in 360 healthy adults who were not occupationally exposed to EtO was measured with a gas chromatograph/mass spectrometer in the electron-capture negative chemical ionization mode. This parameter was correlated with smoking habits and urinary cotinine concentration, exhibiting a positive relationship between HOEtVal and the number of cigarettes smoked (r2 = .4416). Urinary cotinine measurements also correlated with HOEtVal and the number of cigarettes smoked. This positive correlation between urinary cotinine and HOEtVal (r2 = .3893) provides a new perspective on the early stages of carcinogenic processes.

Effect of maternal smoking on ventilatory responses to changes in inspired oxygen levels in infants.

Maternal smoking is a major independent risk factor for sudden infant death syndrome (SIDS). Respiratory control deficits have been implicated in SIDS. The aim of this study was to test the hypothesis that infants born to smoking mothers have reduced ventilatory responses to changes in inspired oxygen. Smoking and nonsmoking women were recruited in midpregnancy and smoking status confirmed by measurement of urinary cotinine. To control for confounding factors of smoking each mother-infant pair in the smoking group was matched to a pair in the nonsmoking group for social class, maternal age and parity, feeding, birthweight, gestational age, and infant sex. Infants were seen overnight at approximately 10 wk of age for tests of respiratory control, using the alternating breath test. Ventilation was measured by respiratory inductance plethysmography and inspired and end-tidal oxygen levels were determined by mass spectrometry. Data were obtained from 40 infants (17 in the smoking group). Responses were similar in both groups for 10 respiratory parameters including respiratory drive and timing, and there were no significant differences. The mean end-tidal oxygen level when 40% O(2) was delivered was an average of 1.13% higher in the smoking group (p = 0.0067), although the inspired oxygen levels were not different. In conclusion, we did not find an independent effect of maternal smoking on respiratory control. The differences in end-tidal oxygen levels during the alternating breath test may represent differences in alveolar ventilation.

Étude du tabagisme passif par la mesure de la cotininurie en consultation de protection maternelle et infantile dans le Nord-Pas-de-Calais

The aim of the study was to determine the circumstances of exposure to environmental tobacco smoke, to evaluate its importance by measurement of urinary cotinine, and to study the relationship with the children's medical history. It was a prospective investigation realized in 20 outpatient pediatric clinics. The parents answered a questionnaire to assess the child's exposure as well as the child's medical and surgical history. Cotinine was measured in urine samples collected during the visit. Concentrations > 6 ng/mL were considered to be positive. Two hundred and one children were included in the study (mean age 17 months, extremes: 1-72 months), 107 of whom were exposed to environmental tobacco smoke. Urinary cotinine was found to be positive in 27 cases (13%). There was a positive relation between passive tobacco exposure and positive urinary cotinine (P < 0.001). Eighty of 201 mothers and 135 of 185 fathers smoked. There was a relation between positive urinary cotinine and the mother's smoking, as well as with a history of upper respiratory tract infection (rhinitis, otitis media) or adenoidectomy. No relation was found between a history of bronchiolitis and passive smoking. Passive tobacco exposure is very frequently encountered in our region. Urinary cotinine, which can be easily measured, might constitute an efficient tool in order to convince the parents of the reality of passive smoking.

Measuring environmental tobacco smoke exposure in infants and young children through urine cotinine and memory-based parental reports: empirical findings and discussion

OBJECTIVEThis study examined the reliability and potential biases of two urine collection methods from which cotinine measures were obtained and the validity of memory-based parental reports of their children's exposure...

Biological monitoring exposure of workers from plant producing carbon electrodes: quantification of benzo[a]pyrene DNA-adducts in leukocytes, by a 32P-postlabelling method and an immunoassay.

The levels of benzo[a]pyrene were monitored for blood DNA-benzo[a]pyrene adducts in 17 workers from a plant producing carbon electrodes, with high exposure to benzo[a]pyrene (575-902-1149 ng m(-3)). Two different techniques, a 32P-postlabelling method and a competitive immunoassay using polyclonal antibodies obtained from rabbits immunised with DNA modified by benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide were used. For each worker, urinary 1-hydroxypyrene, a potential indicator of exposure to polycyclic aromatic hydrocarbons, was measured. The effect of tobacco by urinary cotinine measurement was also considered. The postlabelling and immunoassay detection limits for DNA-benzo[a]pyrene adducts were respectively 0.15 and 10 fmol 50 microg(-1) of DNA. The results obtained by the two methods demonstrated a good detection of DNA-benzo[a]pyrene adducts, but no direct relationship between the quantity of adducts and the concentration of benzo[a]pyrene in air-borne was noted in the studied plant. The levels of DNA-benzo[a]pyrene adducts obtained by immunoassay were significantly higher than those obtained by the 32P-postlabelling (P < 0.001). For several workers, variations due to professional or non professional factors must be taken into account in interpreting the results. In conclusion, the two methods used proved very efficient in determining DNA-benzo[a]pyrene adducts, and may be useful in monitoring human exposure to known and previously unidentified environmental genotoxic agents.

Cytogenetic monitoring in coke oven workers

Cytogenetic markers (chromosomal aberrations, sister chromatid exchanges (SCE), cells with high frequency of SCE (HFC), the heterogeneity index SCE (SCE-H) and genetic polymorphism of genotypes GSTM1 and NAT2 were evaluated in the peripheral lymphocytes of 64 coke oven workers and 34 control subjects from the same plant. Personal monitors were used to evaluate exposure to eight carcinogenic (polycyclic aromatic hydrocarbons) PAHs, including B[a]P, during an 8-h working shift. Smoking habits were checked by urinary cotinine measurement. The exposure among coke oven workers ranged widely from 0.6 to 547 μg/m 3 and 2 to 50 137 ng/m 3, for carcinogenic PAHs and B[ a]P, respectively. The respective values in controls were 0.07 to 1.51 μg/m 3 and from 2 to 63 ng/m 3. The results of biomonitoring in exposed vs. control subjects were as follows: frequency of chromosomal aberrations (% AB.C.), 2.30% AB.C. vs. 1.09% AB.C. ( P<0.05); sister chromatid exchanges, 7.47 SCE/cell vs. 5.49 SCE/cell ( P<0.05); HFC, 5.94% vs. 2.06% ( P<0.05) and SCE-H index, 1.49 vs. 1.01 ( P<0.05). All the cytogenetic markers were significantly increased in the exposed vs. control groups. The effect of smoking was observed only in SCE when evaluated as HFC. Using individual exposure data for carcinogenic PAHs, a significant correlation between exposure and %AB.C. ( r=0.372, P=0.0002), SCE/cell ( r=0.331, P=0.001), HFC ( r=0.467, P=0.007) and SCE/H ( r=0.286, P=0.004) was found. No effects of GSTM1 and NAT2 genotypes, individually or in combination, on the cytogenetic markers was observed. It is concluded that occupational exposure of coke oven workers involved in this study resulted in an increased level of chromosomal aberrations and SCE. The frequency of AB.C. and SCE/cell was found to be related to exposure to carcinogenic PAHs.

Possible interaction between exposure to environmental tobacco smoke and therapy in children with asthma

1. The aim of the study was to determine the carbachol and albuterol responsiveness in treated and untreated asthmatic and allergic children exposed to environmental tobacco smoke assessed by urinary cotinine measurements. 2. Forty-six asthmatic and allergic children with normal spirometric values were recruited. The doubling dose, concentration of carbachol producing a 2-fold increase in specific airway resistance (SRaw) was determined and 200 micrograms of albuterol were administered via a Volumatic(R) spacer. The percentage of bronchodilatation was defined as the difference between the largest obtained SRaw and the post-beta2 SRaw divided by the largest SRaw. Data were compared by a Mann-Whitney U-test. 3. The 23 children with a high urinary cotinine, compared with the 23 children without urinary cotinine, had a decreased doubling dose (108.2+/-14.7 micrograms versus 160.9+/-19.5 micrograms; P=0.04) and an increased percentage of bronchodilatation (74.8+/-1.4% versus 68.8+/-1.8%; P=0.03). A prophylactic anti-inflammatory treatment induced a weaker bronchial reactivity to carbachol and a slightly greater bronchodilatation in children exposed to environmental tobacco smoke. 4. Environmental tobacco smoke increases bronchial reactivity in asthmatic and allergic children. This effect might be reduced by anti-inflammatory therapy. The bronchodilator response may be enhanced in exposed children and may be caused by one or several direct interactions between tobacco smoke compounds and albuterol.

Objective assessment of smoking habits by urinary cotinine measurement in adolescents and young adults with type 1 diabetes. Reliability of reported cigarette consumption and relationship to urinary albumin excretion.

To examine the relationship of objective smoking status to age, sex, longterm metabolic control, and urinary albumin excretion. Patients with type 1 diabetes who smoke are at increased risk to develop diabetic microvascular and macrovascular complications. While this has repeatedly been demonstrated in adults, smoking habits have rarely been investigated in adolescents. Urinary continine excretion has been determined by radioimmunoassay in 238 adolescents and young adults with type 1 diabetes. This biochemical parameter of nicotine use was related to age, to the number of cigarettes allegedly consumed per day, and to urinary albumin excretion. A total of 46 patients (19.3%) with urinary cotinine values > 500 ng/ml were classified as smokers. In 26 patients (10.9%), cotinine values between 100 and 500 ng/ml were found (infrequent smokers or environmental nicotine exposure), while the remaining 166 patients excreted < 100 ng/ml of cotinine in the urine (nonsmokers). Smokers were significantly older (20.2 +/- 0.6 years [mean +/- SE]) compared with the intermediate group (18.3 +/- 0.7 years) or with nonsmokers (15.9 +/- 0.4 years; P < 0.0001, Wilcoxon's signed-rank test). Of 46 smokers, 12 denied smoking cigarettes entirely, and among biochemically defined smokers, no correlation was present between urinary continine excretion and the reported number of cigarettes consumed per day. Urinary albumin excretion was significantly higher in smokers compared with nonsmokers (P < 0.003). These data demonstrate that cigarette smoking is common among German adolescents and young adults with type 1 diabetes in this study. Many patients deny nicotine use or refuse to disclose their smoking habits. Increased urinary albumin excretion is consistent with an increased risk of nephropathy in subjects with diabetes who smoke. Pediatricians in charge of adolescents with type 1 diabetes should actively discuss the risk of nicotine consumption with their patients.

Rapid method for the simultaneous measurement of nicotine and cotinine in urine and serum by gas chromatography–mass spectrometry

A simple, sensitive, and rapid gas chromatographic–mass spectrometric method is described for the simultaneous detection and quantitation of nicotine and its metabolite, cotinine, in urine and serum. The analytes and their respective deuterated internal standards were extracted by liquid–liquid extraction coupled to centrifugation and evaporation. The detection limit of the assay was 0.16 ng/ml for both nicotine and cotinine. The limit of quantitation for each analyte was 1.25 ng/ml.

Intervening to Reduce Environmental Tobacco Smoke Exposure in Infants

The literature search performed by Wall and his associates in conjunction with their study1 failed to identify a randomized intervention trial carried out by our group several years ago, aimed at reducing infant exposure to environmental tobacco smoke(ETS).2 In common with Wall's study, our trial was carried out in primary care offices and used a low-impact intervention strategy. Our study was different, however, in that the infants' interpreted urine cotinine measurements were incorporated into the intervention and were also used to assess ETS exposure in the cases and controls.

Maternal smoking during pregnancy. Effects on lung function during the first 18 months of life.

The present investigation evaluated the effects of maternal smoking during pregnancy on the growth of lung function during the first 18 mo of life in 159 infants who were part of a longitudinal study of the effects of maternal smoking on respiratory health. Infant pulmonary function was assessed at 2 to 6 wk of age and at 4 to 6, 9 to 12, and 15 to 18 mo of age by partial expiratory flow-volume curves and helium dilution FRC. Maternal smoking was assessed by standard questionnaire and urine cotinine measurements. Maternal smoking during pregnancy was associated with a reduction of 9.4 +/- 4.3 ml (p = 0.029) for FRC and 33 +/- 12.3 ml/s (p = 0.008) reduction for flow at FRC (VFRC) after controlling for the effects of growth (length). The effect of maternal smoking was greater for female infants than for male infants. At 1 yr female infants exposed in utero were predicted to have a 16% reduction in VFRC compared with 5% for male infants. No sex difference was seen for FRC or VFRC/FRC. Exposure to environmental tobacco smoke in the postnatal period was not significantly related to reduced FRC or VFRC. These data provide further evidence that maternal smoking during pregnancy may play a greater role than postnatal and childhood exposure on the observed effects on lung function in children.

Objective passive-smoking indicators and respiratory morbidity in young children

Exposure to environmental tobacco smoke is associated with increased respiratory morbidity in young children, but few studies have assessed such exposure objectively by urinary cotinine measurements. 501 children aged 1-5 years, a random 5% sample of children attending an outpatient clinic, were classified as exposed or non-exposed to environmental tobacco smoke with a cut-off of 10 ng cotinine per mg creatinine in urine. Exposed children were 3·5 times (95% Cl 1·56-7·90, p<0·0024) more likely to have increased respiratory morbidity (three or more episodes during the previous 12 months) than non-exposed children after adjustment for potential confounding factors.

PARENTAL SMOKING, URINARY COTININE, AND WHEEZING BRONCHITIS IN CHILDREN

We conducted a case-control study to assess the role of exposure to environmental tobacco smoke (ETS) in the development of wheezing bronchitis in children. The study included 199 children age 4 months to 4 years, who were treated in hospital for wheezing bronchitis, and 351 population controls of the same age group. We estimated exposure to ETS from urinary cotinine measurements as well as from questionnaires to parents. The median urinary cotinine concentration was 5.7 micrograms per liter in cases and 4.4 micrograms per liter in controls. Breast-feeding was related to urinary cotinine excretion in children with smoking mothers. The risk of wheezing bronchitis increased in relation to parental smoking and urinary cotinine concentration. This effect was most prominent in children up to 18 months of age, among whom the relative risk was 3.3 in those with a urinary cotinine level exceeding 20 micrograms per liter (95% confidence interval = 1.5-7.6). Our data confirm that ETS is an important risk factor for wheezing bronchitis in children and indicate that a single urinary cotinine measurement offers no major advantages to questionnaire data for assessment of long-term exposure to ETS.

Beneficial effects of smoking cessation on the short-term prognosis for variant angina — validation of the smoking status by urinary cotinine measurements

To examine whether smoking cessation would improve the short-term prognosis for patients with variant angina, 37 smokers with variant angina who were discharged after the complete disappearance of angina by medical treatment with calcium blockers were advised to stop smoking and were followed-up for 1 year. Urinary cotinine radioimmunoassay was used to evaluate their current smoking status. Patients with a urinary cotinine concentration above 50 ng/ml were classified as current smokers. The prevalence of smokers was underestimated by self-reports (11% by self-reports vs. 35% by urinary cotinine measurements after 3 months; 17% by self-reports vs. 36% by urinary cotinine measurements after 1 year). The presence of angina during the first 3 months was significantly ( P < 0.05) more prevalent in those who continued to smoke ( 8 13 , 62%) than in those who succeeded in smoking cessation ( 5 24 , 21%) when the current smoking status was determined by urinary cotinine measurements. Smoking cessation definitely improved the prognosis for variant angina even during a relatively short follow-up period.

Replacing creatinine measurements with specific gravity values to adjust urine cotinine concentrations

Creatinine and specific gravity (relative density) measurements both allow differences in urine concentration to be taken into account in determining urine cotinine concentrations. In this study we demonstrate that the variance of urine cotinine measurements is reduced comparably when either creatinine or specific gravity measurements are used for correction. This reduction in variability improves the correlation between urine cotinine measurements and clinical endpoints. In this study, the clinical endpoints were pulmonary function in a population of nonsmoking children with asthma, 42% of whom were reported to have been exposed to environmental tobacco smoke. When corrected by either creatinine measurements or specific gravity values, the urine cotinine measurements performed as well or better than reported exposure (and comparably with each other) in assessments of lung function. A dose-response relationship was also more consistently apparent. Specific gravity values can be used reliably in place of creatinine values to adjust urine cotinine measurements for both research and clinical purposes.

Augmentation of smoking cessation education by urinary cotinine measurement.

Monitoring the current smoking status by an objective method may augment the effects of smoking cessation instruction. To quantitatively evaluate smoking status and its modification by smoking cessation instruction, urinary cotinine, a major metabolite of nicotine, was measured by radioimmunoassay in 64 patients with a smoking habit before and during smoking cessation instruction. Urinary cotinine levels were used to discriminate between smokers and nonsmokers (with 50 ng/ml used as a threshold). In 49 patients who claimed to have stopped smoking, urinary cotinine concentrations 1 month after instruction indicated that only 30 (61%) of them had actually stopped (before: 243 +/- 104, after: 1 +/- 3 ng/ml) (mean +/- standard deviation). In the remaining 15 patients who failed to stop smoking while reporting a reduction of cigarette consumption (before: 27 +/- 12, after: 7 +/- 5/day), there was no appreciable reduction in urinary cotinine levels (before: 298 +/- 140, after: 229 +/- 171 ng/ml). When the patients who had failed to stop smoking again received intensive smoking cessation instruction, the success rate increased from 47% (30/64) to 69% (44/64) (p < 0.05). Thus, urinary cotinine measurement may provide a useful and quantitative method for monitoring actual smoking habits and thus augment the efficacy of smoking cessation educational programs.

Urinary cotinine measurement in patients with Buerger's disease[mdash ]Effects of active and passive smoking on the disease process

Urinary cotinine measurement in patients with Buerger's disease[mdash ]Effects of active and passive smoking on the disease process